Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination

Background: The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model. Methodology/Principal Findings: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 mg HA per dose) included rg-A/Vietnam/1203/ 2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 mg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60 % in single A/Anhui/1/2005 vaccine group. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination agains

A Dominant X-Linked QTL Regulating Pubertal Timing in Mice Found by Whole Genome Scanning and Modified Interval-Specific Congenic Strain Analysis

BACKGROUND: Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which differed significantly in the pubertal timing. Vaginal opening (VO) was used to characterize pubertal timing in female mice, and the age at VO of all female mice (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the F1 intercrosses to identify quantitative trait loci (QTLs) controlling this trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM, LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL contributed 2.1 days to the timing of VO, which accounted for 32.31% of the difference between the original strains. Further study showed that the QTL was B6-dominant and explained 10.5% of variation to this trait with a power of 99.4% at an alpha level of 0.05.The location of the significant ChrX QTL found by genome scanning was then fine-mapped to a region of approximately 2.5 cM between marker DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified interval-specific congenic strains (mISCSs). CONCLUSIONS/SIGNIFICANCE: Such findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty, and also reveal the fact that chromosome X (the sex chromosome) does carry gene(s) which take part in the regulative pathway of the pubertal timing in mice

Deviations in palatal region between indirect and direct digital models: an in vivo study

Abstract Background Studies focusing on accuracy of intraoral digital models in the palatal region are scarce. The present study aimed to investigate the influence of different scanning sequences on palatal trueness and to assess deviation and distribution character of trueness in palate. Methods Overall, 35 participants accepted three types of procedures to acquire upper digital models. Indirect models digitalised from plaster models were considered as the reference. Two direct digital models were acquired using TRIOS 3 POD intraoral scanners, namely Groups Tr1 and Tr2, wherein intraoral scanning differed in terms of palatal scanning sequences. Based on a modified dental-level superimposition method, 3D measurements of trueness in palate and palatal vault region (PVR) for palatal stable regional superimposition in Groups Tr1 and Tr2, respectively, were performed. Absolute deviations were measured for trueness, while signed deviations were analysed for shape distortion. Colour-coded maps were used for quantitative analysis of deviation distribution pattern. Paired t test was used to analyse differences in palatal trueness between different scanning sequences. One-way repeated-measures analysis of variance and Bonferroni test were used to compare trueness measurements among different superimposition methods. Intraclass correlation coefficient (ICC) was used to verify reproducibility of the proposed method. Results Palatal trueness in Group Tr1 (118.59 ± 37.67 μm) was slightly less accurate than that (108.25 ± 33.83 μm) in Group Tr2 (p = 0.012  0.90. Conclusions Scanning sequences can affect palatal trueness. Palatal scanning should be initiated at the palatal side of the posterior teeth where the initial scan begins. For 3D PVR superimposition, distal boundary of the selected region should be adjusted mesially whilst referring to intraoral digital models. Trial registration The trial has been registered (registration No: R000039467, Trial ID: UMIN000034617, date of registration: 2018/10/24‘retrospectively registered’)

Further Inequalities involving the Khatri-Rao Product

AbstractStyan [G.P.H. Styan, Hadamard products and multivariate statistical analysis. Linear Algebra and Its Appl. 6 (1973) 217–240] established an inequality involving the Hadamard product using statistical reasoning in the context of multivariate analysis. In this paper, the inequality is extended to involve the Khatri-Rao product in the non-negative definite matrix case and in the non-singular Hermitian matrix case. The equality conditions for these extensions are given. Also established are counterpart inequalities in the positive definite matrix case

The miR-1224-5p/ELF3 Axis Regulates Malignant Behaviors of Pancreatic Cancer via PI3K/AKT/Notch Signaling Pathways

Purpose: Aberrant expression of microRNAs contributes to the progression of pancreatic cancer by targeting downstream genes. A novel regulatory axis, miR-1224-5p/ELF3, was identified by bioinformatic analysis and experimental verification. Studies of the underlying molecular mechanisms behind this axis lead to a better understanding of the development of pancreatic cancer. Materials and Methods: The differential expression of miR-1224-5p and ELF3 was verified based on Gene Expression Omnibus (GEO) datasets and clinical samples. The relationship between miR-1224-5p and ELF3 was demonstrated by luciferase assay and Western blot. The related signaling pathways of the miR-1224-5p/ELF3 axis in pancreatic cancer were investigated by gene set enrichment analysis (GSEA) and verified by Western blot. An analysis between ELF3 expression and immune infiltration was performed. Cellular and animal experiments were utilized to explore the effects of miR-1224-5p and ELF3 in pancreatic cancer. Results: Suppressed expression of miR-1224-5p in pancreatic tumor tissues and cancer cells was identified first. Furthermore, miR-1224-5p is correlated with clinicopathological features, and decreased expression of miR-1224-5p indicates poor prognosis. miR-1224-5p serves as a tumor suppressor and inhibits malignant behaviors of pancreatic cancer based on in vivo and in vitro assays. The putative target gene ELF3 was predicted by bioinformatic analysis and confirmed by dual-luciferase reporter assay. Overexpression of ELF3 can improve the malignant behaviors of pancreatic cancer and demonstrates poor prognosis and advanced clinical stage. The inhibitory role of miR-1224-5p in pancreatic cancer is manifested by its direct targeting of ELF3. A negative correlation between ELF3 expression and immune cell infiltration was identified, suggesting an immunosuppressive state resulting from ELF3 overexpression. The PI3K/AKT/Notch signaling pathways and epithelial-to-mesenchymal transition (EMT) are important underlying mechanisms. Conclusion: The miR-1224-5p/ELF3 axis may serve as a new diagnostic, therapeutic, and prognostic biomarker in pancreatic cancer. The related PI3K/AKT/Notch/EMT signaling pathways greatly promote the elucidation of the progression of pancreatic cancer

an empirical study on bug assignment automation using chinese bug data

Univ SE Calif, Ctr Syst & Software Engn, ABB, Microsoft Res, IEEE, ACMSIGSOFT, N Carolina State Univ Comp SciBug assignment is an important step in bug life-cycle management. In large projects, this task would consume a substantial amount of human effort. To compare with the previous studies on automatic bug assignment in FOSS (Free/Open Source Software) projects, we conduct a case study on a proprietary software project in China. Our study consists of two experiments of automatic bug assignment, using Chinese text and the other non-text information of bug data respectively. Based on text data of the bug repository, the first experiment uses SVM to predict bug assignments and achieve accuracy close to that by human triagers. The second one explores the usefulness of non-text data in making such prediction. The main results from our study includes that text data are most useful data in the bug tracking system to triage bugs, and automation based on text data could effectively reduce the manual effort

a case study on usage of a software process management tool in china

Nowadays, commercial or in-house customized process management tools have been prevalently adopted for supporting software project management and process improvement. In this paper we report a case study to empirically investigate and evaluate the usage status and implications of a supporting tool named QONE in industrial environment in China. Decision theory is adopted in study design. The analysis is mainly based on the usage data from a typical industrial project. Further questionnaires and follow-up interviews with the end-users are also conducted. The analysis results reveal that 1) the effects of such supporting tool vary with respect to different task types, 2) tasks with smaller granularity are comparatively easier to predict and control, 3) missing data reporting analysis helps to reveal opportunities for further process improvement and tool enhancement. This investigation aims to help us take advantages of such supporting tools and benefit software development eventually

Harnessing the Reactivity of Iridium Hydrides by Air: Iridium-Catalyzed Oxidation of Aldehydes to Acids in Water

An iridium-catalyzed oxidation of aldehydes to acids was realized by using air as the oxidant and water as the solvent in the presence of base. Interestingly, the same type of catalysts were also used for the reduction of aldehydes under acidic conditions. A common iridium hydride intermediate is proposed for both redox reactions. The oxidation has a number of advantages such as high yields, great functionality tolerance, and easy purification without chromatography